398 research outputs found

    Fear of Fantasy

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    A review of Thomas W Laqueur's Solitary Sex: A Cultural History of Masturbation (Zone Books, New York, 2003)

    Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.

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    AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells. METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.This work was supported by the European Foundation for the Study of Diabetes and Boehringer Ingelheim Basic Research Programme; the Wellcome Trust (grants 106262/Z/14/Z, 106263/Z/14/Z and 100574/ Z/12/Z); the Medical Research Council Metabolic Diseases Unit (grants MRC_MC_UU_12012/3 and MRC_MC_UU_12012/5); and the Novo Nordisk Foundation

    Evaluation of the implementation of a state government community design policy aimed at increasing local walking: Design issues and baseline results from RESIDE, Perth Western Australia

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    Objectives. To describe the design and baseline results of an evaluation of the Western Australian government's pedestrian-friendly subdivision design code (Liveable Neighborhood (LN) Guidelines). Methods. Baseline results (2003–2005) from a longitudinal study of people (n=1813) moving into new housing developments: 18 Liveable, 11 Hybrid and 45 Conventional (i.e., LDs, HDs and CDs respectively) are presented including usual recreational and transport related walking undertaken within and outside the neighborhood, and 7-day pedometer steps. Results. At baseline, more participants walked for recreation and transport within the neighborhood (52.6%; 36.1% respectively), than outside the neighborhood (17.7%; 13.2% respectively). Notably, only 20% of average total duration of walking (128.4 min/week (SD159.8)) was transport related and within the neighborhood. There were few differences between the groups' demographic, psychosocial and perceived neighborhood environmental characteristics, pedometer steps, or the type, amount and location of self-reported walking ( pN0.05). However, asked what factors influenced their choice of housing development, more participants moving into LDs reported aspects of their new neighborhood's walkability as important ( pb0.05). Conclusions. The baseline results underscore the desirability of incorporating behavior and context-specific measures and value of longitudinal designs to enable changes in behavior, attitudes, and urban form to be monitored, while adjusting for baseline residential location preferences

    Patterns of mortality in domesticated ruminants in Ethiopia

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    BACKGROUND: Premature death of livestock is a problem in all ruminant production systems. While the number of premature ruminant deaths in a country is a reasonable indicator for the nation's health, few data sources exist in a country like Ethiopia that can be used to generate valid estimates. The present study aimed to establish if three different data sets, each with imperfect information on ruminant mortality, including abortions, could be combined into improved estimates of nationwide mortality in Ethiopia. METHODS: We combined information from a recent survey of ruminant mortality with information from the Living Standards Measurement Study and the Disease Outbreak and Vaccination Reporting dataset. Generalized linear mixed and hurdle models were used for data analysis, with results summarized using predicted outcomes. RESULTS: Analyses indicated that most herds experienced zero mortality and reproductive losses, with rare occasions of larger losses. Diseases causing deaths varied greatly both geographically and over time. There was little agreement between the different datasets. While the models aid the understanding of patterns of mortality and reproductive losses, the degree of variation observed limited the predictive scope. CONCLUSIONS: The models revealed some insight into why mortality rates are variable over time and are therefore less useful in measuring production or health status, and it is suggested that alternative measures of productivity, such as number of offspring raised to 1 year old per dam, would be more stable over time and likely more indicative

    How important is the land use mix measure in understanding walking behaviour? Results from the RESIDE study

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    <p>Abstract</p> <p>Background</p> <p>Understanding the relationship between urban design and physical activity is a high priority. Different representations of land use diversity may impact the association between neighbourhood design and specific walking behaviours. This study examined different entropy based computations of land use mix (LUM) used in the development of walkability indices (WIs) and their association with walking behaviour.</p> <p>Methods</p> <p>Participants in the RESIDential Environments project (RESIDE) self-reported mins/week of recreational, transport and total walking using the Neighbourhood Physical Activity Questionnaire (n = 1798). Land use categories were incrementally added to test five different LUM models to identify the strongest associations with recreational, transport and total walking. Logistic regression was used to analyse associations between WIs and walking behaviour using three cut points: any (> 0 mins), ≥ 60 mins and ≥ 150 mins walking/week.</p> <p>Results</p> <p>Participants in high (vs. low) walkable neighbourhoods reported up to almost twice the amount of walking, irrespective of the LUM measure used. However, different computations of LUM were found to be relevant for different types and amounts of walking (i.e., > 0, ≥ 60 or ≥ 150 mins/week). Transport walking (≥ 60 mins/week) had the strongest and most significant association (OR = 2.24; 95% CI:1.58-3.18) with the WI when the LUM included 'residential', 'retail', 'office', 'health, welfare and community', <it>and </it>'entertainment, culture and recreation'. However, any (> 0 mins/week) recreational walking was more strongly associated with the WI (OR = 1.36; 95% CI:1.04-1.78) when land use categories included 'public open space', 'sporting infrastructure' and 'primary and rural' land uses. The observed associations were generally stronger for ≥ 60 mins/week compared with > 0 mins/week of transport walking and total walking but this relationship was not seen for recreational walking.</p> <p>Conclusions</p> <p>Varying the combination of land uses in the LUM calculation of WIs affects the strength of relationships with different types (and amounts) of walking. Future research should examine the relationship between walkability and specific types and different amounts of walking. Our results provide an important first step towards developing a context-specific WI that is associated with recreational walking. Inherent problems with administrative data and the use of entropy formulas for the calculation of LUM highlight the need to explore alternative or complimentary measures of the environment.</p

    The influence of urban design on neighbourhood walking following residential relocation : longitudinal results from the RESIDE study

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    The design of urban environments has the potential to enhance the health and well-being of residents by impacting social determinants of health including access to public transport, green space and local amenities. Commencing in 2003, RESIDE is a longitudinal natural experiment examining the impact of urban planning on active living in metropolitan Perth, Western Australia. Participants building homes in new housing developments were surveyed before relocation (n = 1813; 34·6% recruitment rate); and approximately 12 months later (n = 1437). Changes in perceived and objective neighbourhood characteristics associated with walking following relocation were examined, adjusted for changes in demographic, intrapersonal, interpersonal and baseline reasons for residential location choice. Self-reported walking was measured using the Neighbourhood Physical Activity Questionnaire. Following relocation, transport-related walking declined overall (p &lt; 0.001) and recreational walking increased (p &lt; 0.001): access to transport- and recreational destinations changed in similar directions. However, in those with increased access to destinations, transport-related walking increased by 5.8 min/week for each type of transport-related destination that increased (p = 0.045); and recreational walking by 17.6 min/week for each type of recreational destination that increased (p = 0.070). The association between the built environment and recreational walking was partially mediated by changes in perceived neighbourhood attractiveness: when changes in ‘enjoyment’ and ‘attitude’ towards local walking were removed from the multivariate model, recreational walking returned to 20.1 min/week (p = 0.040) for each type of recreational destination that increased. This study provides longitudinal evidence that both transport and recreational-walking behaviours respond to changes in the availability and diversity of local transport- and recreational destinations, and demonstrates the potential of local infrastructure to support health-enhancing behaviours. As neighbourhoods evolve, longer-term follow-up is required to fully capture changes that occur, and the impact on residents. The potential for using policies, incentives and infrastructure levies to enable the early introduction of recreational and transport-related facilities into new housing developments warrants further investigation

    Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery

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    Objectives Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. Design A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, 80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. Results PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. Conclusion The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.Peer reviewe

    RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

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    BACKGROUND: People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? METHODS/DESIGN: This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. DISCUSSION: This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. TRIAL REGISTRATION: ISRCTN62019087.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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